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Genome-wide association analysis of metabolic traits in a birth cohort from a founder population

Genome-wide association analysis of metabolic traits in a birth cohort from a founder population
Genome-wide association analysis of metabolic traits in a birth cohort from a founder population
Genome-wide association studies (GWAS) of longitudinal birth cohorts enable joint investigation of environmental and genetic influences on complex traits. We report GWAS results for nine quantitative metabolic traits (triglycerides, high-density lipoprotein, low-density lipoprotein, glucose, insulin, C-reactive protein, body mass index, and systolic and diastolic blood pressure) in the Northern Finland Birth Cohort 1966 (NFBC1966), drawn from the most genetically isolated Finnish regions. We replicate most previously reported associations for these traits and identify nine new associations, several of which highlight genes with metabolic functions: high-density lipoprotein with NR1H3 (LXRA), low-density lipoprotein with AR and FADS1-FADS2, glucose with MTNR1B, and insulin with PANK1. Two of these new associations emerged after adjustment of results for body mass index. Gene-environment interaction analyses suggested additional associations, which will require validation in larger samples. The currently identified loci, together with quantified environmental exposures, explain little of the trait variation in NFBC1966. The association observed between low-density lipoprotein and an infrequent variant in AR suggests the potential of such a cohort for identifying associations with both common, low-impact and rarer, high-impact quantitative trait loci
WEB/URL: PM:19060910;
genetics, blood, birth, quantitative trait loci, triglycerides, report, gene, body mass index, insulin, exposure, analysis, pressure, human, environmental, finland, c-reactive protein, statistics, cohort, protein, glucose, genes, population, blood pressure, environmental exposure, association
1061-4036
35-46
Sabatti, Chiara
cd0e1cdf-37ab-4b0c-9e0f-2ddb2dfa52f8
Service, Susan K
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Hartikainen, Anna-Liisa
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Pouta, Anneli
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Ripatti, Samuli
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Brodsky, Jae
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Jones, Chris G.
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Zaitlen, Noah A
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Varilo, Teppo
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Kaakinen, Marika
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Sovio, Ulla
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Ruokonen, Aimo
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Laitinen, Jaana
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Jakkula, Eveliina
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Coin, Lachlan
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Hoggart, Clive
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Collins, Andrew
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Turunen, Hannu
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Gabriel, Stacey
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Elliot, Paul
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McCarthy, Mark I
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Daly, Mark J
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Jarvelin, Marjo-Riitta
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Freimer, Nelson B
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Peltonen, Leena
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Sabatti, Chiara
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Service, Susan K
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Hartikainen, Anna-Liisa
f3af50ad-2846-4220-9cf8-9c535b9dd908
Pouta, Anneli
108c5aa1-3b41-4095-91fa-ecd523934370
Ripatti, Samuli
705fa391-c779-4941-814c-8ce1f8fbefb7
Brodsky, Jae
a54376e1-d358-43b7-bc1c-ff78ae5c8296
Jones, Chris G.
bb590beb-4219-4897-858c-c99a721b4bf3
Zaitlen, Noah A
9eac8160-96b2-4eab-bc99-dcadba9a75ae
Varilo, Teppo
c52c9f49-afa7-4242-ad11-1e51808a5117
Kaakinen, Marika
25c15795-fcf9-43df-ad64-e29cb9107985
Sovio, Ulla
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Ruokonen, Aimo
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Laitinen, Jaana
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Jakkula, Eveliina
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Coin, Lachlan
ff460121-4ac3-40f0-8f72-546ac0485023
Hoggart, Clive
cf1c9469-2c64-4ce9-848c-558a7a873c41
Collins, Andrew
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Turunen, Hannu
1f576712-5c93-4d25-83f2-dab5e15a4566
Gabriel, Stacey
77bff238-8fb4-401c-b7dc-bb4ca4d1b7fb
Elliot, Paul
bb1ffa6e-e5ae-4117-9d50-e1d7906ca418
McCarthy, Mark I
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Daly, Mark J
a193c6c7-5369-48f9-8783-b9e1449e4dfb
Jarvelin, Marjo-Riitta
54bf0cc8-8f32-47db-b22d-6e694f1c1b26
Freimer, Nelson B
d3ce5455-8965-4b2f-b544-01be10de5340
Peltonen, Leena
416f8c0d-5e92-47be-bf10-94006bb1292e

Sabatti, Chiara, Service, Susan K, Hartikainen, Anna-Liisa, Pouta, Anneli, Ripatti, Samuli, Brodsky, Jae, Jones, Chris G., Zaitlen, Noah A, Varilo, Teppo, Kaakinen, Marika, Sovio, Ulla, Ruokonen, Aimo, Laitinen, Jaana, Jakkula, Eveliina, Coin, Lachlan, Hoggart, Clive, Collins, Andrew, Turunen, Hannu, Gabriel, Stacey, Elliot, Paul, McCarthy, Mark I, Daly, Mark J, Jarvelin, Marjo-Riitta, Freimer, Nelson B and Peltonen, Leena (2009) Genome-wide association analysis of metabolic traits in a birth cohort from a founder population. Nature Genetics, 41 (1), 35-46. (doi:10.1038/ng.271). (PMID:19060910)

Record type: Article

Abstract

Genome-wide association studies (GWAS) of longitudinal birth cohorts enable joint investigation of environmental and genetic influences on complex traits. We report GWAS results for nine quantitative metabolic traits (triglycerides, high-density lipoprotein, low-density lipoprotein, glucose, insulin, C-reactive protein, body mass index, and systolic and diastolic blood pressure) in the Northern Finland Birth Cohort 1966 (NFBC1966), drawn from the most genetically isolated Finnish regions. We replicate most previously reported associations for these traits and identify nine new associations, several of which highlight genes with metabolic functions: high-density lipoprotein with NR1H3 (LXRA), low-density lipoprotein with AR and FADS1-FADS2, glucose with MTNR1B, and insulin with PANK1. Two of these new associations emerged after adjustment of results for body mass index. Gene-environment interaction analyses suggested additional associations, which will require validation in larger samples. The currently identified loci, together with quantified environmental exposures, explain little of the trait variation in NFBC1966. The association observed between low-density lipoprotein and an infrequent variant in AR suggests the potential of such a cohort for identifying associations with both common, low-impact and rarer, high-impact quantitative trait loci
WEB/URL: PM:19060910;

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More information

e-pub ahead of print date: 7 December 2008
Published date: January 2009
Keywords: genetics, blood, birth, quantitative trait loci, triglycerides, report, gene, body mass index, insulin, exposure, analysis, pressure, human, environmental, finland, c-reactive protein, statistics, cohort, protein, glucose, genes, population, blood pressure, environmental exposure, association
Organisations: Medicine

Identifiers

Local EPrints ID: 70786
URI: http://eprints.soton.ac.uk/id/eprint/70786
ISSN: 1061-4036
PURE UUID: ddb92f3b-bc3f-4677-9a8e-024ba9c808e2
ORCID for Andrew Collins: ORCID iD orcid.org/0000-0001-7108-0771

Catalogue record

Date deposited: 06 Jan 2010
Last modified: 14 Mar 2024 02:35

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Contributors

Author: Chiara Sabatti
Author: Susan K Service
Author: Anna-Liisa Hartikainen
Author: Anneli Pouta
Author: Samuli Ripatti
Author: Jae Brodsky
Author: Chris G. Jones
Author: Noah A Zaitlen
Author: Teppo Varilo
Author: Marika Kaakinen
Author: Ulla Sovio
Author: Aimo Ruokonen
Author: Jaana Laitinen
Author: Eveliina Jakkula
Author: Lachlan Coin
Author: Clive Hoggart
Author: Andrew Collins ORCID iD
Author: Hannu Turunen
Author: Stacey Gabriel
Author: Paul Elliot
Author: Mark I McCarthy
Author: Mark J Daly
Author: Marjo-Riitta Jarvelin
Author: Nelson B Freimer
Author: Leena Peltonen

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